- Boiling point:975.6±65.0 °C(Predicted)
- Density 1.161
- Flash point:543.8℃
- CAS DataBase Reference868540-17-4
- HS Code 29337900
Carfilzomib is an irreversible proteasome inhibitor and antineoplastic agent.The mechanism of action of carfilzomib is as a Proteasome Inhibitor, Carfilzomib irreversibly binds to and inhibits the chymotrypsin-like activity of the 20S catalytic core subunit of the proteasome, a protease complex responsible for degrading a large variety of cellular proteins. Inhibition of proteasome-mediated proteolysis results in an accumulation of polyubiquinated proteins, which may lead to cell cycle arrest, induction of apoptosis, and inhibition of tumor growth.
Carfilzomib is used in treatment of refractory multiple myeloma. Carfilzomib is associated with a low rate of serum enzyme elevations during treatment and has been implicated to rare instances of clinically apparent, acute liver injury some of which have been fatal.
Carfilzomib is a second-generation, irreversible, peptide epoxyketone class proteasome inhibitor that targets the chymotrypsin-like β5 subunit of the constitutive 20S proteasome (IC50 = 5.2 nM) and the β5i subunit of the immunoproteasome 20Si (LMP7; IC50 = 14 nM) with minimal cross reactivity to other proteases. It can induce cell cycle arrest and apoptosis in human cancer cell lines including multiple myeloma, lymphoma, and various solid tumors (IC50s = 2.4-20 nM).
- MechanismCarfilzomib is a tetrapeptide-based epoxy-proteasome inhibitor that irreversibly binds to the 20S proteasome containing the threonine N-terminal active site and the in vivo proteolysis core particle of 26S proteasome. In animal, carfilzomib has antiproliferative and apoptosis activity in vitro in solid and hematological granulocytes. In animals, carfilzomib inhibits proteasome activity in blood and tissue and delays tumor growth in multiple myeloma, hematological and solid tumor models.
- Side effectsThe most common adverse events observed in clinical trials (incidence ≥30%) were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea and fever; the most common serious adverse events (overall incidence 45%) include pneumonia, acute renal failure, fever and congestive heart failure.
- Efficacy and SafetyTo assess the safety and efficacy of the drug, one study included 266 patients who had received at least two prior therapies, including bortezomib and thalidomide. It was assessed of the complete or partial disappearance of the tumor in the treated patient (overall response rate). The overall response rate was 23% and the median response time was 7.8 months.
Common adverse effects of carfilzomib were observed in more than 30% of the subjects include fatigue, low blood cell counts and platelet counts, dyspnea, diarrhea and fever. Severe adverse reactions include heart failure and dyspnea. Upon the occurrence of serious adverse reactions, the patient should be closely monitored and stop the drug treatment.
Information regarding the pharmacological effects, indications, mechanism of action, indications and side effects of Carfilzomib, a drug for treating multiple myeloma (MM), were compiled and edited by Xiao Nan of ChemicalBook.
In July 2012, the US FDA approved carfilzomib (also referred to as PR-171) for the treatment of patients with multiple myeloma (MM) who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression within 60 days of completion of the last therapy. Carfilzomib binds to and irreversibly inhibits the chymotrypsin-like protease activity of the constitutive proteosome (β5) and immunoproteosome (β5i) via its epoxyketone pharmacophore. Proteosome inhibition results in the accumulation of polyubiquitinated proteins and induction of apoptosis through activation of both the intrinsic and extrinsic caspase pathways. Carfilzomib inhibits chymotrypsin activity with an IC50 of 6 nM and is less potent an inhibitor of trypsin and caspase (IC50s of 3600 and 2400 nM, respectively). Cell cycle arrest and apoptosis are seen in a variety of hematologic and solid tumor cell lines (e.g.,MM, acutemyeloid leukemia (AML), pancreatic cancer, lung cancer) treated with carfilzomib. The synthesis of carfilzomib is reported in the patent literature and a route to the intermediate epoxy ketone from a Boc-leucine-derived α,β-unsaturated ketone is also described.
- Chemical PropertiesWhite Solid
- OriginatorProteolix Inc. (United States)
- UsesCarfilzomib is a second-generation proteasome inhibitor that is used as a treatment in relapsed and refractory multiple myeloma.
- DefinitionChEBI: A synthetic tetrapeptide consisting of morpholin-4-acetyl, L-2-amino-4-phenylbutanoyl, L-leucyl and L-phenylalanyl residues joined in sequence with the C-terminus connected to the amino group of (2<element S)-2-amino-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-1-one via an amide linkage. Used for the treatment of patients with multiple myeloma
- brand nameKyprolis
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